DESCRIPTION (Applicant's Description): The objective of this training program i s to produce young scientists qualified to make original research contributions in the chemical sciences related to cancer, both its prevention and treatment by chemotherapy. Ten faculty members of the Chemistry Department constitute the core research team around which the educational offerings of the program are built. Predoctoral candidates admitted to the program first complete a rigorous selection of courses and examinations after which they concentrate in one of several available research areas, also available to postdoctoral trainees, for their Ph.D. dissertation. Included in this offering are projects in the molecular basis of carcinogenesis, mechanistic studies of anticancer drugs, the synthesis of new antitumor agents including combinatorial chemistry, and new approaches to chemotherapeutic intervention through the study of cell surfaces and signal transduction. A new requirement has been introduced that postdoctoral associates take one course of direct relevance to cancer biology. Specific projects include cellular responses to DNA damage; mechanistic and synthetic studies of platinum anticancer drugs; chemical methods for the analysis of carcinogen metabolism; DNA damage, carcinogenesis and molecular biomarkers for cancer epidemiology; purine biosynthesis as an appropriate target for new antitumor agents; inhibitors of ribonucleotide reductases; bleomycins and enediynes as antitumor antibiotics; synthetic and biochemical studies of heparin-like glycosaminoglycans; the use of the fumagillin family of natural products as probes; the development of general synthetic methodology appropriate for combinatorial chemistry and rapid throughput screening; and strategies to prepare anticancer agents. In addition to their research, graduate and postdoctoral students in the program are required to expand their knowledge through participation in a regularly scheduled seminar program and by travel to key scientific meetings. At MIT, trainees present their research results, listen to presentations by their colleagues, and hear a variety of lectures by c a n c er researchers in the greater Boston community. Included are epidemiologists and clinical oncologists as well as basic scientists, to give the trainees a comprehensive picture of the roles of environmental factors in the etiology of cancer and of chemotherapy in the prevention and clinical management of the disease. At national and international meetings, members of the training grant give papers and attend sessions on work related to their own project as well as the projects of others on the training grant. Their experiences are then related to other trainees in the program upon returning to MIT. Education in the proper conduct of science and in scientific ethics is required through assigned readings and participation in regularly scheduled sessions with the faculty in which case studies are presented and discussed.